The ability of liposomes to encapsulate pharmacological agents thereby sequestering them from the surrounding medium, together with their potential for site-specific delivery in vivo, has stimulated interest in their use as drug carriers for enhancing therapeutic index.
Intravenously administered liposomes generally become associated with organs of the reticuloendothelial system, mainly the liver and spleen, a distribution shared with other intravenously injected colloids and suspensions. This tendency restricts the ability of liposomes to be directed to specific target tissues.
Liposomes were first produced in England in 1965 according to the July/August 1981 issue of Prospectus. They are easily made in the laboratory from common, low cost material such as egg lecithin.
The literature is replete with reports of studies directed to attempts to target the liposomes to a specific cell or organ, in order to avoid having the medication taken up by the entire system. However, only a very few reports of actual success to limited systems are known. One specific example of success was reported at a California conference on new medical technology sponsored by Robert S. First, Inc., White Plains, N.Y. It was reported that treatment of tropical parasitic disease Leishmaniasis is based on derivatives of antimony. The problem is that doses of antimony strong enough to kill the parasite may also kill the patient.
Liposomes technology provides a novel treatment of the disease for two simple reasons. First, it is known that the parasite is found entirely in the cells that make up one branch of the immune system known as the reticuloendothelial system which will hereafter be referred to as RES. Secondly, liposomes injected intravenously are cleared from the blood by these varied RES cells. In one experiment, liposomes were loaded with an antimony compound and injected into rats that had been infected with the parasite. Examination of the rats livers revealed that drugs delivered via the liposomes totally destroyed the parasites.
This success is due to the fact that the RES recognizes liposomes and by taking the liposomes from the blood system and dismantling the lipid cover, exposes the very infected areas to strong doses of the antimony compounds which could not be tolerated in the entire system.
It is important to note that the reticuloendothelial system may inhibit efforts to use liposomes for treatment because the RES will scavenge the liposomes.
Therefore, it is an object of this invention to produce a liposome which is masked from recognition by the RES.
Another object of the invention is to produce a biochemical membrane covered with sialic acid residues thereby providing a coating that masks the surface of the membrane from recognition by the scavenging cells of the body much like the surface of a red blood cell is masked from scavenging cell recognition and uptake during its circulating lifetime.